Photocatalytic sequential C–H functionalization expediting acetoxymalonylation of imidazo heterocycles

• Deepak Singh,
• Shyamal Pramanik and
• Soumitra Maity

Beilstein J. Org. Chem. 2023, 19, 666–673, doi:10.3762/bjoc.19.48

• investigation revealed a sequential sp2 and sp3 C–H activation, followed by functionalization driven by zinc acetate coupled with the photocatalyst PTH. A variety of imidazo[1,2-a]pyridines and related heterocycles were explored as substrates along with several active methylene reagents, all generating the

• products with excellent yields and regioselectivity, thus confirming excellent functional group tolerability. Keywords: C–H functionalization; imidazo heterocycles; photoredox; regioselective; relay catalysis; Introduction Among all N-fused heterocycles, imidazo[1,2-a]pyridines (IPs) are the prevalent

• moieties in several bioactive pharmaceuticals and natural products [1][2][3][4]. Moreover, due to their susceptibility towards 'exited-state intramolecular proton transfer' phenomena, IPs are also effective in optoelectronics and materials sciences [5][6]. C-3-functionalized imidazo[1,2-a]pyridines are

Transition-metal-catalyzed C–H bond activation as a sustainable strategy for the synthesis of fluorinated molecules: an overview

• Louis Monsigny,
• Floriane Doche and
• Tatiana Besset

Beilstein J. Org. Chem. 2023, 19, 448–473, doi:10.3762/bjoc.19.35

• trifluoromethylthiolation of azacalix[1]arene[3]pyridines by C–H bond activation using a complex of Cu(ClO4)2·6H2O and the shelf-stable Me4NSCF3 [115][116] as a nucleophilic source of SCF3 (Scheme 3) [100]. Within these conditions, a set of six azacalix[1]arene[3]pyridines bearing electron-donating groups, halogens or

• % yields, respectively. This reaction proved to be compatible with the presence of an ester (8c) or a halogen (8e). Other directing groups, such as substituted pyridines (9a and 9b) and pyrimidine (9c) turned out to be also efficient in this transformation (Scheme 5, 4 examples, up to 84% yield). The same

• ) were found to be suitable substrates leading to the corresponding products 12h and 12i in 91% and 83% yields, respectively. The use of other directing groups was also suitable for this transformation such as methyl and cyano-substituted pyridines 13a,b, pyrimidine (13c), pyrazole (13d), as well as the

Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• application scope, robustness, and selectivity [74]. Recently, an electrochemical NHPI/PINO-mediated benzylic iodination was achieved using lutidine or 2,6-di-tert-butylpyridine as bases with low nucleophilicity [89] (Scheme 10). When pyridine was used instead 2,6-disubstituted pyridines its N-benzylation by

A new route for the synthesis of 1-deazaguanine and 1-deazahypoxanthine

• Raphael Bereiter,
• Marco Oberlechner and
• Ronald Micura

Beilstein J. Org. Chem. 2022, 18, 1617–1624, doi:10.3762/bjoc.18.172

• pyrrolopyrimidines) are N-heterocycles that have become an indispensable part of research in medicinal chemistry [1][2][3]. Especially, derivatives of 3-deazaguanine (imidazo[4,5-c]pyridines) [4], 7-deazaguanine/-hypoxanthine (pyrrolo[2,3-d]pyrimidines) [5][6], and 9-deazaguanine/-hypoxanthine (pyrrolo[3,2-d

• , glycogen synthase kinase 3 (GSK-3), leucine-rich repeat kinase 2 (LRRK2), tyrosine phosphorylation-regulated kinase-1A (DYRK1A) and CDC2-like kinase 1 (CLK1), and fatty acid amide hydrolase (FAAH) [4]). Similar properties were ascertained for 1-deazapurine derivatives (imidazo[4,5-b]pyridines) and

Dienophilic reactivity of 2-phosphaindolizines: a conceptual DFT investigation

• Nosheen Beig,
• Aarti Peswani and
• Raj Kumar Bansal

Beilstein J. Org. Chem. 2022, 18, 1217–1224, doi:10.3762/bjoc.18.127

• -diazaphospholo[1,2-a]pyridines, i.e., 1-aza-2-phosphaindolizines 3 [2], 1,2,3-diazaphospholo[1,5-a]pyridines, i.e., 3-aza-2-phosphaindolizines 4 [3], and 1,2,4,3-triazaphospholo[1,5-a]pyridine, i.e., 1,3-diaza-2-phosphaindolizine (5, Figure 2) [4]. We succeeded in developing another method involving a 1,5

Synthesis of novel alkynyl imidazopyridinyl selenides: copper-catalyzed tandem selenation of selenium with 2-arylimidazo[1,2-a]pyridines and terminal alkynes

• Mio Matsumura,
• Kaho Tsukada,
• Kiwa Sugimoto,
• Yuki Murata and
• Shuji Yasuike

Beilstein J. Org. Chem. 2022, 18, 863–871, doi:10.3762/bjoc.18.87

• reaction between terminal alkynes and diimidazopyridinyl diselenides, generated from imidazo[1,2-a]pyridines and Se powder, using 10 mol % of CuI and 1,10-phenanthroline as the catalytic system under aerobic conditions. The C(sp2)–Se and C(sp)–Se bond-formation reaction can be performed in one-pot by using

• reagents and 1,3-dipolar azide–alkyne cycloaddition based on the alkyne moiety. Keywords: alkynyl imidazopyridinyl selenide; copper catalyst; imidazo[1,2-a]pyridine; selenium; tandem reaction; terminal alkyne; Introduction Imidazo[1,2-a]pyridines are important heterocycles that serve as key functional

• groups in many biologically active substances and pharmaceuticals, such as zolpidem, alpidem, and GSK812397 [1][2][3]. Therefore, the development of multiple chemical modification methods, at the 3-position of the imidazo[1,2-a]pyridine skeleton, for the synthesis of 3-substituted-imidazo[1,2-a]pyridines

Heteroleptic metallosupramolecular aggregates/complexation for supramolecular catalysis

• Prodip Howlader and
• Michael Schmittel

Beilstein J. Org. Chem. 2022, 18, 597–630, doi:10.3762/bjoc.18.62

• ]. Since at a given time, only one of both HETPYP-bound pyridines in [Cu4(76)2]4+ can serve as axle, the rotor undergoes a domino rotation that was measured to occur at k298 = 142 kHz. For the heteromeric rotor [Cu2(53)(76)]2+, two orthogonal dynamic interactions are relevant, i.e., the weak Npy → ZnPor

Syntheses of novel pyridine-based low-molecular-weight luminogens possessing aggregation-induced emission enhancement (AIEE) properties

• Masayori Hagimori,
• Tatsusada Yoshida,
• Yasuhisa Nishimura,
• Yukiko Ogawa and
• Keitaro Tanaka

Beilstein J. Org. Chem. 2022, 18, 580–587, doi:10.3762/bjoc.18.60

• electron-withdrawing groups [13][14][15]. Previously, we have reported various pyridine derivatives, including polysubstituted pyridines and fused pyridines, which exhibited strong fluorescence in organic solvents (ethanol and dichloromethane) [16][17][18][19], while their fluorescence in aqueous media was

• heterocyclic compounds, such as ring-fused pyridines (pyrido[1,2-a]pyrrolo[3,4-d]pyrimidines) and secondary aminopyridines (N-methyl-4-((pyridin-2-yl)amino)-substituted maleimides), by changing the substituents at position 5 of the 2-aminopyridine. Interestingly, among these pyridine derivatives, secondary

Synthesis of novel [1,2,4]triazolo[1,5-b][1,2,4,5]tetrazines and investigation of their fungistatic activity

• Anna V. Korotina,
• Svetlana G. Tolshchina,
• Rashida I. Ishmetova,
• Natalya P. Evstigneeva,
• Natalya A. Gerasimova,
• Natalya V. Zilberberg,
• Nikolay V. Kungurov,
• Gennady L. Rusinov,
• Oleg N. Chupakhin and
• Valery N. Charushin

Beilstein J. Org. Chem. 2022, 18, 243–250, doi:10.3762/bjoc.18.29

• particular, imidazo[1,2-a]pyridines and imidazo[1,2-a]pyrimidines exhibit a wide spectrum of biological activity, including antiviral and antibacterial ones [1][2]. A promising approach for the development of new drugs is the synthesis and bioscreening of high nitrogen-containing azoloazines, including azolo

Direct C(sp³)–H allylation of 2-alkylpyridines with Morita–Baylis–Hillman carbonates via a tandem nucleophilic substitution/aza-Cope rearrangement

• Siyu Wang,
• Lianyou Zheng,
• Shutao Wang,
• Shulin Ning,
• Zhuoqi Zhang and
• Jinbao Xiang

Beilstein J. Org. Chem. 2021, 17, 2505–2510, doi:10.3762/bjoc.17.167

• ; Morita–Baylis–Hillman carbonates; Introduction Pyridines are among the most important heterocyclic structural moieties in many biologically active natural products, pharmaceuticals, and agrochemicals [1][2][3]. Therefore, the development of efficient strategies for functionalized pyridine derivatives

Recent advances in the tandem annulation of 1,3-enynes to functionalized pyridine and pyrrole derivatives

• Yi Liu,
• Puying Luo,
• Yang Fu,
• Tianxin Hao,
• Xuan Liu,
• Qiuping Ding and
• Yiyuan Peng

Beilstein J. Org. Chem. 2021, 17, 2462–2476, doi:10.3762/bjoc.17.163

• or ligand in organic chemistry [6][7][8][9][10]. Therefore, the development of efficient methods for the synthesis of pyridine derivatives has attracted considerable attention [11][12][13][14]. The industrial synthetic methods of pyridines mainly involve: i) extraction from coal tar; ii) condensation

• powerful nitrogen source for the synthesis of various N-heterocycles, such as isoquinolines, quinolines, pyridines, pyrroles, indoles, azoles, and azepines [40][41][42][43][44][45]. 1,3-Enyne, as a powerful Michael acceptor, is a wonderful synthon for the synthesis of N-heterocycles via tandem addition and

• functionalized pyridines and pyrroles. Review Synthesis of pyridines via tandem annulation of 1,3-enynes In 2015, Reddy and co-workers reported the synthesis of substituted pyridines via Lewis acid-mediated aza-annulation of 2-en-4-ynyl azides 1 (Scheme 1) [49]. They discovered that Ag-mediated intramolecular

Halides as versatile anions in asymmetric anion-binding organocatalysis

• Lukas Schifferer,
• Martin Stinglhamer,
• Kirandeep Kaur and
• Olga García Macheño

Beilstein J. Org. Chem. 2021, 17, 2270–2286, doi:10.3762/bjoc.17.145

• diastereoselective glycosylation reaction. b) Competing SN1 vs SN2 reactivity. a) Folding mechanism of oligotriazoles upon anion recognition. b) Representative tetratriazole 82 catalyzed enantioselective Reissert-type reaction of quinolines and pyridines with various nucleophiles. Switchable chiral tetratriazole

Development of N-F fluorinating agents and their fluorinations: Historical perspective

• Teruo Umemoto,
• Yuhao Yang and
• Gerald B. Hammond

Beilstein J. Org. Chem. 2021, 17, 1752–1813, doi:10.3762/bjoc.17.123

• -4j < unsubstituted 4a < 3,5-diCl 4t < 2,6-diCl 4r < pentachloro 4v, in good agreement with the decreasing order of the pKa values of the pyridines. For example, in order to fluorinate phenol, triMe 5-4j needed heating at 100 °C in a haloalkane solvent for 24 h, whereas pentachloro 5-4v required only

• these reagents exhibited a low reactivity due to their low solubility in organic solvents [32]. Their fluorinating power increased in the order of 18-2a < 2b ≈ 2c ≈ 2d ≈ 2e < 2f < 2g < 2h, consistent with the order of the pKa values of the pyridines (Scheme 39). The least powerful 18-2a was suitable for

Icilio Guareschi and his amazing “1897 reaction”

• Gian Cesare Tron,
• Alberto Minassi,
• Giovanni Sorba,
• Mara Fausone and
• Giovanni Appendino

Beilstein J. Org. Chem. 2021, 17, 1335–1351, doi:10.3762/bjoc.17.93

• achieved fame in the realm of organic chemistry [33]. The availability of novel and spacious laboratories is associated with the most important contributions of Guareschi to organic chemistry, those on piperidines and pyridines. His first article in the area appeared already in 1891 [34] and the last one

• and by the one of Fileti on cyanamide. At least five different reactions are pooled under the name “Guareschi or Guareschi–Thorpe synthesis of pyridines”, and considerable confusion exists in the literature that apparently makes no distinction between the various reactions (Scheme 4). Part of the

• . Their ideas had a strong influence on Guareschi, who, after first supporting the organic origin of oil, later became a moderate supporter of the abiogenic theory. The first publication on pyridines appeared while Guareschi was actively contributing to the first edition of the Italian Pharmacopoeia

Application of the Meerwein reaction of 1,4-benzoquinone to a metal-free synthesis of benzofuropyridine analogues

• Rashmi Singh,
• Tomas Horsten,
• Rashmi Prakash,
• Swapan Dey and
• Wim Dehaen

Beilstein J. Org. Chem. 2021, 17, 977–982, doi:10.3762/bjoc.17.79

• example of a biologically active benzofuropyridine is revamilast (7), which has been used in Phase II clinical trials, studying the treatment of asthma and rheumatoid arthritis [19]. Other examples are the hydroxybenzofuro[2,3-b]pyridines 8 with efflux pump inhibitory activity useful in chemotherapy [20

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

• functionalized dihydro-1H-pyrazolo[3,4-b]pyridines 99 under the same conditions. Moreover, the reaction preceded well even with other 1,3-diketones along with primary heterocyclic amines (Scheme 36). The modest yields of 99 compared to 97 were reasoned with the decomposition of the amines. Suprisingly, the

• rearrangement [102] in an analogous heterocyclic system. 8 Pyridines/fused pyridines 8.1 Pyridines Pyridines are six-membered ring systems consisting of five carbon atoms and one nitrogen atom. Highly substituted pyridines are known to show various pharmacological activities and are also found in various

• the microwave-assisted synthesis of steroidal pyridines 123 utilizing steroidal ketones 122, aldehydes 5, malononitrile (51)/methyl cyanoacetate and ammonium acetate as structural units and MgO nanoparticles as a catalyst in ethanol solvent. The reaction proceeded even in absence of a catalyst but

Synthesis of β-triazolylenones via metal-free desulfonylative alkylation of N-tosyl-1,2,3-triazoles

• Soumyaranjan Pati,
• Renata G. Almeida,
• Eufrânio N. da Silva Júnior and
• Irishi N. N. Namboothiri

Beilstein J. Org. Chem. 2021, 17, 762–770, doi:10.3762/bjoc.17.66

• precursors in denitrogenative transannulation reactions under metal-catalysed conditions to form other heterocycles such as functionalized pyrroles, imidazoles and pyridines (Scheme 1b) [11][12][13]. The traditional method for the synthesis of triazole unit is the Huisgen 1,3-dipolar cycloaddition between

Unexpected rearrangements and a novel synthesis of 1,1-dichloro-1-alkenones from 1,1,1-trifluoroalkanones with aluminium trichloride

• Beatrice Lansbergen,
• Catherine S. Meister and
• Michael C. McLeod

Beilstein J. Org. Chem. 2021, 17, 404–409, doi:10.3762/bjoc.17.36

• %. Naphthalene 6h and 2-pyridine 6i were also successfully obtained, however, the reactions with the 3- and 4-pyridines 5j and 5k resulted in complex mixtures from which no desired product, nor starting material, could be observed. The scope of this chemistry also extends to substrates with a shorter

Decarboxylative trifluoromethylthiolation of pyridylacetates

• Ryouta Kawanishi,
• Kosuke Nakada and
• Kazutaka Shibatomi

Beilstein J. Org. Chem. 2021, 17, 229–233, doi:10.3762/bjoc.17.23

• synthesizing substituted pyridines are in high demand in pharmaceutical and agricultural chemistry [1][2]. Because of the unique features of fluorine atoms, fluorinated functional groups have also been recognized as important substructures in the design of medicinally relevant compounds [3][4][5][6

An atom-economical addition of methyl azaarenes with aromatic aldehydes via benzylic C(sp³)–H bond functionalization under solvent- and catalyst-free conditions

• Divya Rohini Yennamaneni,
• Vasu Amrutham,
• Krishna Sai Gajula,
• Rammurthy Banothu,
• Murali Boosa and
• Narender Nama

Beilstein J. Org. Chem. 2020, 16, 3093–3103, doi:10.3762/bjoc.16.259

• to 4-nitrobenzaldehyde (2a). The product of this is the intermediate B, which favors the formation of the corresponding desired product 3a, as shown in Scheme 5. Conclusion In summary, this work provides a green and simple synthetic methodology for the synthesis of higher azaarenes from pyridines and

• clean process. A variety of aromatic aldehydes, including electron-donating, electron-withdrawing, as well as halogen groups was screened, affording the products in moderate to excellent yields. Azaarenes such as pyridines with various substitution patterns and a few quinolines were also reacted with

Regioselective synthesis of heterocyclic N-sulfonyl amidines from heteroaromatic thioamides and sulfonyl azides

• Vladimir Ilkin,
• Vera Berseneva,
• Tetyana Beryozkina,
• Tatiana Glukhareva,
• Lidia Dianova,
• Wim Dehaen,
• Eugenia Seliverstova and
• Vasiliy Bakulev

Beilstein J. Org. Chem. 2020, 16, 2937–2947, doi:10.3762/bjoc.16.243

• formation of tar-like products. 2,5-Bis(N-sulfonylamidino)pyridines Bis(thioamide) 1p containing a pyridine ring was found to react with sulfonyl azides 2a,c–f either in boiling propanol or in the absence of a solvent to form compounds 3aj–an bearing two N-sulfonyl amidine fragments connected to a pyridine

Synthesis of imidazo[1,5-a]pyridines via cyclocondensation of 2-(aminomethyl)pyridines with electrophilically activated nitroalkanes

• Dmitrii A. Aksenov,
• Nikolai A. Arutiunov,
• Vladimir V. Maliuga,
• Alexander V. Aksenov and
• Michael Rubin

Beilstein J. Org. Chem. 2020, 16, 2903–2910, doi:10.3762/bjoc.16.239

• , USA 10.3762/bjoc.16.239 Abstract Imidazo[1,5-a]pyridines were efficiently prepared via the cyclization of 2-picolylamines with nitroalkanes electrophilically activated in the presence of phosphorous acid in polyphosphoric acid (PPA) medium. Keywords: cyclization; heterocycles; imidazo[1,5-a

• ]pyridines; nitroalkanes; polyphosphoric acid; Introduction It is hard to overstate the importance of imidazo[1,5-a]pyridines in modern organic and medicinal chemistry. Several natural alkaloids possessing this core were isolated from marine sponges, for example, cribrostatin 6 (Figure 1) [1][2][3]. The

• development of efficient synthetic methods to access imidazo[1,5-a]pyridines, with more than 120,000 individual compounds prepared to date. Most synthetic approaches rely on various cyclocondensations of nucleophilic (2-aminomethyl)pyridine precursors, introducing a new five-membered ring. Typically

One-pot multicomponent green Hantzsch synthesis of 1,2-dihydropyridine derivatives with antiproliferative activity

• Giovanna Bosica,
• Kaylie Demanuele,
• José M. Padrón and
• Adrián Puerta

Beilstein J. Org. Chem. 2020, 16, 2862–2869, doi:10.3762/bjoc.16.235

• contributions. As a result, such research has grown exponentially in the past decade [5][6]. The work conducted by the German chemist Arthur Hantzsch exploded in the synthetic interest in dihydropyridines and pyridines when the pharmacological usefulness of these compounds in medicine was discovered [7]. The

• source of nitrogen has also been varied from the classical use of ammonia. The most common nitrogen source reported in literature is ammonium acetate (3). Others include the use of oxahydrazines, primary amines, and urea. The oxidation of dihydropyridines to pyridines has been achieved using mild

Synthesis of 4-substituted azopyridine-functionalized Ni(II)-porphyrins as molecular spin switches

• Jannis Ludwig,
• Tobias Moje,
• Fynn Röhricht and
• Rainer Herges

Beilstein J. Org. Chem. 2020, 16, 2589–2597, doi:10.3762/bjoc.16.210

• state. 4-Substituted pyridines exhibit a distinguished correlation between basicity and coordination strength as axial ligands with Ni-porphyrins [12]. Hence, Hammet σ values might be used to predict and to systematically optimize the performance of the spin switch. In previous studies we have shown

• diamagnetic (or the paramagnetic) species in the two photostationary states. The intermolecular association constants of pyridines as axial ligands to Ni-porphyrins as a function of their para substituents usually follow the Hammett relationship [5][12]. Hence, the association constants should also be

• notorious problem of porphyrin-based spin switches. To kill two birds with one stone, we introduced acidic substituents in 4-position of the pyridines (1h (R = SH), 1j (R = COOH)). Deprotonation to the corresponding anions should increase the coordination power of the pyridine and increase the solubility of

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

• reaction to proceed. Jiang et al. developed a similar system for the enantioselective radical addition into 2-vinylazaarenes 122 using DPZ and either α-amino radicals [60] or ketyl radicals [61], with pyridines being well tolerated as substrates in this latter case (Scheme 17a). The same group also